T cell immunity is crucial in defense against intracellular pathogens and in surveillance of tumors. The long-term goal of these studies is to understand the mechanism of T cell activation in vivo and to determine what constitutes a memory cell. Immunological memory remains one of the most fascinating but least understood aspects of the immune system. One of the major obstacles in studying T cell memory has been the inability to isolate "pure" populations of in vivo selected memory cells. We have recently developed a system that overcomes this problem: We have shown that virus specific CD8+cytotoxic T lymphocytes (CTL) can persist indefinitely in vivo, and that it is possible to isolate "pure" populations of these memory T cells. The objectives of the proposed research are as follows: 1.To determine the fine specificity (viral epitope) and T cell receptor (TCR) usage of the long-lived virus specific CD8+CTL. 2.To examine lymphokine production during in vivo activation of these memory CTL. 3.To determine if immunological memory is dependent on the persistence of antigen (i.e., does survival of memory CTL depend on the presence of antigen). 4.To determine the life span, antigen requirements, and lymphokine production of virus specific memory CD4+T helper cells. These studies should lead to an improved fundamental understanding of immunological memory and T cell activation in vivo. In addition, the proposed studies may have some bearing on the development of effective vaccination strategies, and on the treatment of chronic infections.